Abstract

MicroRNAs (miRNAs) have emerged as potential therapeutic targets for non-alcoholic fatty liver disease/non-alcoholic steatohepatitis (NAFLD/NASH). Traditional Chineses Medicine (TCM) plays an important role in the prevention or treatment of NAFLD/NASH. However, miRNA targets of TCM against NASH still remain largely unknown. Here, we showed that Yiqi-Bushen-Tiaozhi (YBT) recipe effectively attenuated diet-induced NASH in C57BL/6 mice. To identify the miRNA targets of YBT and understand the potential underlying mechanisms, we performed network pharmacology using miRNA and mRNA deep sequencing data combined with Ingenuity Pathway Analysis (IPA). Mmu-let-7a-5p, mmu-let-7b-5p, mmu-let-7g-3p and mmu-miR-106b-3p were screened as the main targets of YBT. Our results suggested that YBT might alleviate NASH by regulating the expression of these miRNAs that potentially modulate inflammation/immunity and oxidative stress. This study provides useful information for guiding future studies on the mechanism of YBT against NASH by regulating miRNAs.

Highlights

  • Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide and the prevalence rate is up to 20–30% (Al-Dayyat et al, 2018)

  • U6 was used as internal reference and three replicates for each sample. mRNA qRT-PCR was performed as we previously described and the β-actin transcripts were used as the internal control (Hong et al, 2019)

  • The total hepatic RNA from mice of normal feeding diet (ND) group (ND for 16 weeks), WD group (Western diet for 16 weeks) and YBT group (Western diet for 16 weeks combined with YBT intervention for 12 weeks) were extracted and subjected to high-throughput sequencing

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Summary

Introduction

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide and the prevalence rate is up to 20–30% (Al-Dayyat et al, 2018). In the absence of intervention, NAFLD may progress from non-alcoholic fatty liver to non-alcoholic steatohepatitis (NASH), which includes liver fibrosis, cirrhosis and hepatocellular carcinoma (HCC) (Konerman et al, 2018). It is found that the pathogenesis of NASH is associated with the imbalance of hepatocyte lipid metabolism, oxidative stress and inflammatory response (Sanyal, 2019). The mechanisms involved in the progression of NASH remain to be elucidated. MicroRNAs (miRNAs) are a class of endogenous, single-stranded non-coding RNAs with the length of ∼22-nt.

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